OBJECTIVES: 1. In the coming year we will perform additional serial studies of endogenous CO production in patients with sickle cell disease in both a steady state and during mild pain crisis. In addition, we have begun a comparative study of red cell life span using 51Cr and CO technic simultaneously and plan to extend the studies to the determination of ineffective erythropoesis and total CO binding capacity in hemolytic v/s normal states. 2. Beta-thalassemia gene has been considered a "controller gene" mutant. If this be true, there should occur crossovers between the controller and the structural locus so that the thalassemia gene controls beta S synthesis. To test this hypothesis we will study globin chain synthesis in SS subjects with MCV less than 90 fl and AS individual with less than 30% hemoglobin S. Family studies will be used to try to sort out the complex proposed genetics. 3. We will extend the study of iron status in sickel cell disease to add free erythrocyte protoporphyrin measurement and bone marrow examination for iron store (some subjects). We will study the effect of iron therapy on ISC count, minimum gelling concentraiton, MCHC and clinical course of the disease, should clinical iron deficiency be found. 4. The effect of more strenous exercise on endogenous CO production will be studied in normal healthy adults. With a more graded degree of exercise, similar studies are planned in healthy sickle cell trait subjects as well. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as a result of this application.